DNA viruses

Cause cutaneous vesicular eruptions and are transmitted through contact with oral or genital secretions or direct contact with actively infected vesicle.

HSV 1 is most often associated with oral-labial lesions and HSV 2 is associated with genital herpes. 

After exposure, the virus replicates in epithelial cells then travels retrograde up axons where it becomes latent in the sensory ganglia (trigeminal or sacral). Reactivation can be stimulated by stress, trauma, fever, and sunlight. Viruses reactivate in the sensory ganglia and travel anterograde down the sensory nerve where cutaneous eruptions arise in the skin, characterized by non-scarring vesicles. Frequent and recurrent reactivations are commonplace. Asymptomatic viral shedding also occurs and is an important part of human-to-human transmission.

Ocular disease can occur during reactivation in the trigeminal ganglia, leading to keratitis with potential for corneal scarring and vision loss. 

Exposure to genital secretions during birth can lead to HSV-2 transmission to the neonate leading to local ocular or cutaneous disease, CNS infection, and/or disseminated disease with multiorgan failure.

CNS disease can occur in primary or reactivation. HSV-1 causes encephalitis with temporal lobe involvement and high morbidity/mortality. HSV-2 causes a mild aseptic meningitis that can recur with recurrent outbreaks; severe disease is uncommon. 

Diagnosis is often made presumptively based on appearance of typical lesions. Otherwise, identification of organism is usually accomplished by PCR of involved fluid. Tzank smears of the cells from the base of the vesicle is non-specific and not frequently used (but you may still see it in textbooks).

Treatment is acyclovir, valacyclovir. Neither have any effect on latent virus.

Transmitted via respiratory droplets.

Primary infection leads viremia and dissemination and manifests as a diffuse vesicular rash known as chicken pox. The virus then establishes latency in sensory ganglia (dorsal nerve roots, trigeminal ganglia, other cranial nerve roots). Reactivation occurs with advancing age and/or immunosuppression and causes a local vesicular eruption that occurs within the dermatome of involved ganglia, this is called shingles. Reactivation in cranial nerve ganglia can lead to other abnormalities including hearing deficits (Ramsay-hunt), facial nerve paralysis (Bell’s palsy), and ocular involvement with V1 reactivation.

Reactivation of zoster is infrequent, in fact, having more than one episode of shingles is very uncommon. 

Persons with advanced immunosuppression (e.g. stem cell transplant, AIDS) can develop disseminated disease with organ dysfunction during reactivation.

Treatment is with acyclovir or valacyclovir. Higher doses are required compared to HSV.

Vaccination against chickenpox is routine for children. Shingles vaccine is recommended for persons >50years, regardless of varicella vaccination.

Transmitted via oral secretions and is acquired in the first 5 years of life for most humans.

Latency is within lymphoid tissue and CD4 lymphocytes. HHV-6 is well documented cause of exanthem subitum. HHV-7 may cause asymptomatic or mild disease during infection. 

Initial infection causes exanthem subitum (roseola) with 3-days of high fevers, followed by diffuse maculopapular rash that develops at the abrupt resolution of fevers. The high fever makes this a common cause of febrile seizures and is one of the six classic childhood exanthems.

Reactivation is of concern in patients with advanced immunosuppression where it has been associated with graft-vs-host disease and bone marrow suppression. 

No treatment is currently available. 

Least prevalent herpes virus in the United States but prevalence varies geographically. It is endemic in Central African and Mediterranean areas.

It is transmitted via saliva but requires prolonged contact and is linked with intimate contact (such as kissing between sexual partners). HHV-8 latency is primarily within B-cells though a latent and lytic process occurs in other cells. 

Primary infection is asymptomatic, but HHV-8 causes Kaposi sarcoma, a spindle cell tumor of endothelial origins. In the US, this is primarily seen in patients with advanced AIDS; the course is aggressive and life-threatening without immune restoration. Prior to AIDS epidemic, KS cases were predominantly seen in males of Mediterranean or central African origins. Other associated clinical diseases related to HHV-8 are primary effusion lymphoma and multicentric castleman’s disease. 

Treatment options are limited and immune restoration is key. Foscarnet and ganciclovir have anti-viral activity. 

Named for the typical cytopathic effect produced in cell cultures, described as “owl’s eyes.” 

Up to 70% of adults in the US are infected with CMV which usually occurs in the first 5 years of life. CMV can be found in many bodily fluids including saliva and genital secretions. Latent infection occurs in leukocytes and immature leukocytes. 

Clinical findings of acute CMV infection can range from minimally symptomatic to mononucleosis-syndrome.  Reactivation is subclinical in the immunocompetent. More severe disease is found in immunosuppressed conditions, such as pneumonia and hepatitis. In persons with AIDS, CMV reactivation in the eye causes a severe, rapidly progressive retinitis. 

CMV can also be spread transplacentally from mother to fetus and is the most common cause of congenital abnormalities in the US. Disease in the fetus is worse if primary infection occurs during pregnancy (as opposed to asymptomatic reactivation) and infections early in pregnancy carry higher risk of abnormalities. A variety of congenital defects include hepatosplenomegaly, jaundice, cytopenias, low birth weight, microcephaly, and chorioretinitis, hearing loss may be a late manifestation. 

Since asymptomatic lytic phase is common, identification of the organism by PCR in the serum is not always diagnostic and evidence of CMV-related cytopathic changes or PCR of affected tissue are needed. 

Ganciclovir is used to treat serious CMV infections. 

Transmitted via oral secretions and establishes latency in B-lymphocytes.

Primary infection—“Infectious Mononucleosis”—leads to a proliferation of non-specific B-cells and results in fever, pharyngitis, lymphadenopathy. Abundant atypical lymphocytes can be found in peripheral blood and a heterophile antibody (monospot test) is usually present—though both of these findings can be found in other conditions. EBV-specific antibodies develop in sequence after acute infection, the presence of viral capsid antibodies is suggestive of acute infection. 

In its latent form, EBV has oncogenic potential from somewhat unclear mechanisms, but may include immortalization of B-cell close. EBV is associated with:

• • African Burkitt’s lymphoma (due to c-myc translocation)
  • Post-transplant lymphoproliferative disease
  • Nasopharyngeal carcinoma
  • Primary CNS lymphoma in persons with AIDS.  

EBV also causes oral hairy leukoplakia (a benign condition) in persons with AIDS. 

There is no specific antiviral therapy for EBV.